Acción de venenos ofídicos del género Bothrops (yarará) sobre la membrana de eritrocitos de carnero

El estudio de la resistencia globular osmótica (RGO) es importante en la determinación de ciertos problemas clínicos, como así también modificaciones morfológicas de la membrana plasmática del eritrocito. Glóbulos rojos de carneros fueron incubados con veneno de serpientes del género Bothrops (B. diporus, B. jararaca, B. jararacussu, B. moojeni) durante 30 minutos a 37ºC. Posteriormente fueron sometidos a soluciones de NaCl de osmolaridad decreciente (0,85 a 0,20 g/l), incubándose a 4ºC durante un máximo de 3 horas, para luego leer en espectrofotómetro la absorbancia del sobrenadante a 540 nm. Los eritrocitos incubados con los distintos venenos también fueron examinados al microscopio óptico y electrónico de barrido. Todos los venenos ensayados mostraron un comportamiento similar, siendo la RGO mínima de 0,70 g/l de NaCl y la máxima de 0,20 g/l, excepto para el veneno de B. jararacussu que causó hemólisis máxima con 0,50 g/l. La microscopía óptica mostró eritrocitos con poiquilocitosis y espiculados; mayores alteraciones de la membrana plasmática fueron detectadas por microscopía electrónica de barrido. Algunos venenos indujeron daños más severos que otros; en general se registró disminución del tamaño celular, mientras que con el veneno de B. jararacussu la mayoría de las células presentaba destrucción de su membrana. Se resalta que el presente estudio es un ensayo in vitro, y que en un paciente con accidente de mordedura, los eventos ocurren con participación de componentes endógenos que configuran un entorno diferente, facilitando o impidiendo la actividad lítica

Impact of primary kidney disease on the effects of empagliflozin in patients with chronic kidney disease: secondary analyses of the EMPA-KIDNEY trial

Background: The EMPA KIDNEY trial showed that empagliflozin reduced the risk of the primary composite outcome of kidney disease progression or cardiovascular death in patients with chronic kidney disease mainly through slowing progression. We aimed to assess how effects of empagliflozin might differ by primary kidney disease across its broad population. Methods: EMPA-KIDNEY, a randomised, controlled, phase 3 trial, was conducted at 241 centres in eight countries (Canada, China, Germany, Italy, Japan, Malaysia, the UK, and the USA). Patients were eligible if their estimated glomerular filtration rate (eGFR) was 20 to less than 45 mL/min per 1·73 m2, or 45 to less than 90 mL/min per 1·73 m2 with a urinary albumin-to-creatinine ratio (uACR) of 200 mg/g or higher at screening. They were randomly assigned (1:1) to 10 mg oral empagliflozin once daily or matching placebo. Effects on kidney disease progression (defined as a sustained ≥40% eGFR decline from randomisation, end-stage kidney disease, a sustained eGFR below 10 mL/min per 1·73 m2, or death from kidney failure) were assessed using prespecified Cox models, and eGFR slope analyses used shared parameter models. Subgroup comparisons were performed by including relevant interaction terms in models. EMPA-KIDNEY is registered with ClinicalTrials.gov, NCT03594110. Findings: Between May 15, 2019, and April 16, 2021, 6609 participants were randomly assigned and followed up for a median of 2·0 years (IQR 1·5–2·4). Prespecified subgroupings by primary kidney disease included 2057 (31·1%) participants with diabetic kidney disease, 1669 (25·3%) with glomerular disease, 1445 (21·9%) with hypertensive or renovascular disease, and 1438 (21·8%) with other or unknown causes. Kidney disease progression occurred in 384 (11·6%) of 3304 patients in the empagliflozin group and 504 (15·2%) of 3305 patients in the placebo group (hazard ratio 0·71 [95% CI 0·62–0·81]), with no evidence that the relative effect size varied significantly by primary kidney disease (pheterogeneity=0·62). The between-group difference in chronic eGFR slopes (ie, from 2 months to final follow-up) was 1·37 mL/min per 1·73 m2 per year (95% CI 1·16–1·59), representing a 50% (42–58) reduction in the rate of chronic eGFR decline. This relative effect of empagliflozin on chronic eGFR slope was similar in analyses by different primary kidney diseases, including in explorations by type of glomerular disease and diabetes (p values for heterogeneity all >0·1). Interpretation: In a broad range of patients with chronic kidney disease at risk of progression, including a wide range of non-diabetic causes of chronic kidney disease, empagliflozin reduced risk of kidney disease progression. Relative effect sizes were broadly similar irrespective of the cause of primary kidney disease, suggesting that SGLT2 inhibitors should be part of a standard of care to minimise risk of kidney failure in chronic kidney disease. Funding: Boehringer Ingelheim, Eli Lilly, and UK Medical Research Council